Diagnosing Diversity Collapse and Validating Mask-Conditioned Diffusion for Labeled Microtubule Microscopy

Abstract

Mask-conditioned diffusion models have become standard for generating labeled training data in biomedical imaging. But the tools used to evaluate them were built for a different problem. Standard metrics like FID and KID score images through ImageNet-trained features. Those features do not transfer to microscopy, leaving the metrics poorly calibrated for specialized domains. Even with a domain-appropriate feature space, a single blended number can still hide a real failure: a model can produce visually plausible images that still transfer poorly to downstream tasks. We identify a specific failure mode: Late in training, realism keeps improving while texture diversity collapses. The model settles onto a fixed color palette, converging to a high-similarity, low-diversity state that standard metrics do not penalize. Therefore, we propose a diversity-aware diagnostic in a domain-validated feature space. It combines a realism axis based on inter-similarity to real images with a diversity axis based on intra-similarity among generated samples. This diagnostic selects a checkpoint that domain experts cannot reliably distinguish from real recordings in a forced-choice study. It also yields useful downstream segmentation: a segmenter trained only on synthetically labeled data reaches a median skeletonised IoU comparable to one trained on real data, at lower cross-fold variance, and clearly ahead of the best available public alternative in this domain, a parametric renderer. We also reproduce a data-efficient hyperparameter-transfer experiment from prior work, tuning several foundation segmenters on a small labeled subset and evaluating on real images: transfer is stronger with our data. We release DiffuMT on HuggingFace, including the triplet dataset, code to reproduce the downstream-utility validation, and a standalone diagnostic tool for evaluating mask-conditioned diffusion models.